Valoid tablets

Cyclizine Hydrochloride 50 mg Tablets

Tablets containing 50 mg of cyclizine hydrochloride.

Excipient: Lactose.

For a full list of excipients, see section 6.1.

Tablet

White, biconvex, uncoated tablet, scored; coded T4A.

The tablet can be divided into two halves.

Route of administration: oral

Adults and Children over 12 Years:

50 mg orally, which may be repeated up to three times a day.

Children 6 – 12 Years:

25 mg orally, which may be repeated up to three times a day.

Children less than 6 years of age:

Valoid tablets are not recommended for children less than 6 years of age.

Use in the Elderly:

There have been no specific studies of Valoid in the elderly. Experience has indicated that normal adult dosage is appropriate.

To prevent motion sickness Valoid should be taken about one to two hours before departure.

Valoid should not be given to individuals with known hypersensitivity to cyclizine.

As with other anticholinergic agents, Valoid may precipitate incipient glaucoma and it should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy.

Cyclizine should be used with caution in patients with severe heart failure. In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure.

Cyclizine should be avoided in porphyria.

There have been reports of abuse of cyclizine, either oral or intravenous, for its euphoric or hallucinatory effects. The concomitant misuse of Valoid with large amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine may increase the toxicity of alcohol (see also Section 4.5 Interactions).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Valoid may have additive effects with alcohol and other central nervous system depressants e.g. hypnotics, tranquillisers, anaesthetics.

Valoid enhances the soporific effect of pethidine.

Because of its anticholinergic activity cyclizine may enhance the side-effects of other anticholinergic drugs.

In the absence of any definitive human data, the use of Valoid in pregnancy is not advised.

It is not known whether cyclizine or its metabolite are excreted in human milk.

Studies designed to detect drowsiness did not reveal sedation in healthy adults who took a single oral therapeutic dose (50 mg) of cyclizine.

Patients should not drive or operate machinery until they have determined their own response.

Although there are no data available, patients should be cautioned that Valoid may have additive effects with alcohol and other central nervous system depressants, e.g. hypnotics and tranquillisers.

Blood and lymphatic system disorders

Agranulocytosis

Cardiac disorders

Tachycardia

Eye disorders

Blurred vision, oculogyric crisis

Gastrointestinal system disorders

Dryness of the mouth, nose and throat, constipation

General disorders and administration site conditions

Asthenia

Hepatobiliary disorders

Hepatic dysfunction, hypersensitivity hepatitis, cholestatic jaundice and cholestatic hepatitis have occurred in association with cyclizine.

Immune system disorders

Hypersensitivity reactions, including anaphylaxis have occurred

Musculoskeletal and connective tissue disorders

Twitching, muscle spasms

Nervous system disorders

Effects on the central nervous system have been reported with cyclizine these include somnolence, headache, dystonia, dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.

Psychiatric disorders

Disorientation, restlessness, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

Renal and urinary disorders

Urinary retention

Respiratory, thoracic and mediastinal disorders

Bronchospasm, apnoea

Skin and subcutaneous tissue disorders

Urticaria, drug rash, angioedema, allergic skin reactions, fixed drug eruption

Vascular disorders

Hypertension

Symptoms:

Symptoms of acute toxicity from cyclizine arise from peripheral anticholinergic effects and effects on the central nervous system.

Peripheral anticholinergic symptoms include dry mouth, nose and throat, blurred vision, tachycardia and urinary retention. Central nervous system effects include drowsiness, dizziness, incoordination, ataxia, weakness, hyperexcitability, disorientation, impaired judgement, hallucinations, hyperkinesia, extrapyramidal motor disturbances, convulsions, hyperpyrexia and respiratory depression.

An oral dose of 5 mg/kg is likely to be associated with at least one of the clinical symptoms stated above. Younger children are more susceptible to convulsions. The incidence of convulsions, in children less than 5 years, is about 60% when the oral dose ingested exceeds 40 mg/kg.

Treatment:

In the management of acute overdosage with Valoid, gastric lavage and supportive measures for respiration and circulation should be performed if necessary. Convulsions should be controlled in the usual way with parenteral anticonvulsant therapy.

ATC Code: R60AE03

Pharmacotherapeutic Group: Piperazine derivatives

Mode of Action:

Cyclizine is a histamine H₁ receptor antagonist of the piperazine class which is characterised by a low incidence of drowsiness. It possesses anticholinergic and antiemetic properties. The exact mechanism by which cyclizine can prevent or suppress both nausea and vomiting from various causes is unknown. Cyclizine increases lower oesophageal sphincter tone and reduces the sensitivity of the labyrinthine apparatus. It may inhibit the part of the midbrain known collectively as the emetic centre.

Pharmacodynamics:

Cyclizine produces its antiemetic effect within two hours and last approximately four hours.

H₁-blockers are well absorbed from the GI tract. Following oral administration effects develop within 30 minutes, are maximal within 1-2 hours and last, for cyclizine, for 4-6 hours.

In healthy adult volunteers the administration of a single oral dose of 50 mg cyclizine resulted in a peak plasma concentration of approximately 70 ng/mL occurring at about two hours after drug administration. The plasma elimination half-life was approximately 20 hours.

The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine. Norcyclizine has little antihistaminic (H₁) activity compared to cyclizine. It is widely distributed throughout the tissues and has a plasma elimination half-life of approximately 20 hours.

After a single dose of 50 mg cyclizine given to a single adult male volunteer, urine collected over the following 24 hours contained less than 1% of the total dose administered.

A. Mutagenicity:

Cyclizine was not mutagenic in a full Ames test, including use of S9-microsomes but can nitrosate in vitro to form mutagenic products.

B. Carcinogenicity:

No long term studies have been conducted in animals to determine whether cyclizine has a potential for carcinogenesis. However, long-term studies with cyclizine administered with nitrate have indicated no carcinogenicity.

C. Teratogenicity:

Some animal studies are interpreted as indicating that Cyclizine may be teratogenic. The relevance of these studies to the human situation is not known.

D. Fertility:

In a study involving prolonged administration of cyclizine to male and female rats there was no evidence of impaired fertility after continuous treatment for 90-100 days. There is no experience of the effect of Valoid on human fertility.

Lactose

Potato starch

Acacia

Magnesium stearate

None known.

Five years.

Store below 25°C.

Amber glass or polyethylene bottles with polyethylene tamper evident caps for containing 100 tablets.

No special instructions.

Amdipharm PLC

Trading as Amdipharm

Regency House

Miles Gray Road

Basildon

Essex SS14 3AF

United Kingdom

PL 20072/0011

05/12/2005

20/02/2012